Serum LDH Research Articles

Evaluating the Efficacy of Immunotherapy in Fragile Hospitalized Patients

Background: Immunotherapy is the cornerstone of treatment for many cancers. The effectiveness of immunotherapy in hospitalized patients is unknown due to the exclusion of this fragile population from clinical trials. This study evaluates the efficacy of immunotherapy in fragile hospitalized patients. Method: We conducted a single-center retrospective study involving 49 patients who started an immunotherapy (IO) during a hospitalization or within 3 months after a hospitalization at the Centre Hospitalier de l’Université de Sherbrooke (CHUS). Efficacy analysis included objective response rate (ORR), overall survival (OS), and progression-free survival (PFS). Results: Immunotherapy resulted in 30.6% of all grades combined and 18.4% of grade three to four immune-related adverse events (irAE). Efficacy outcomes were inferior in the fragile cohort of patients with ORR of 38.9%, PFS of 2.8 months (95% CI [2.17–3.35]), and OS of 3.2 months (95% CI [1.60–4.84]). Performance status of ECOG three to four compared to ECOG zero predicts poor OS (HR 5.666 [1.207–26.594]; p = 0.028) and PFS (HR 4.136 [0.867–19.733]; p = 0.075). Fitness to receive four to six cycles (HR 0.335 [0.152–0.0.738]; p < 0.007) or more predicts greater OS compared to one to three cycles of immunotherapy. Low levels of serum albumin (HR 0.917 [0.852–0.987]; p = 0.021) and elevated levels of serum LDH (HR 2.224 [1.469–3.367]; p < 0.001) are associated with a reduced OS. Conclusion: The effectiveness of immunotherapy in fragile hospitalized patients is compromised, although they exhibit significant irAE. Excellent performance status, fitness to receive many IO treatments, and normal levels of serum LDH and albumin may be useful in selecting patients who will benefit from immunotherapy.

Approaches to early detection of atypical hemolytic-uremic syndrome after childbirth

Introduction. Differentiating conditions accompanied by the development of thrombotic microangiopathy (TMA) in obstetrics is still rather challenging. Our present opinion is that the effect of childbirth on the TMA symptom regression is the key to differential diagnosis. If hemolysis and thrombocytopenia regress after childbirth, we can talk about HELLP syndrome. If not, we should think about atypical hemolytic uremic syndrome (aHUS). aHUS is an extremely rare disease characterized by TMA predominantly involving acute kidney injury. However, the diagnostic task can also be difficult due to possible overlapping one process with another: for example, HELLP syndrome can trigger aHUS, but which of the patients is more susceptible to this transformation is unclear.Aim. To identify clinical and laboratory criteria that can be used to early detect aHUS immediately after childbirth.Materials and methods. A total of 230 patients were enrolled in the study, of whom 71 women were diagnosed with aHUS, 124 patients with HELLP syndrome, and 35 patients without signs of TMA were enrolled in the control group. We assessed and compared the main clinical, anamnestic and laboratory findings.Results. Women with HELLP syndrome and aHUS were comparable in terms of age, frequency of operative delivery and gestational age at delivery, and adverse perinatal outcomes. Peak serum creatinine and LDH values after delivery were the most useful to early predict aHUS. Serum creatinine > 142 μmol/L and LDH > 1391 U/L were associated with the transformation of HELLP syndrome into aHUS.Conclusion. We concluded that standard laboratory data, most specifically peak serum creatinine and LDH, may be used to aid in the early diagnosis of aHUS.

Dan-shen Yin attenuates myocardial fibrosis after myocardial infarction in rats: molecular mechanism insights by integrated transcriptomics and network pharmacology analysis and experimental validation

Ethnopharmacological relevanceDan-shen Yin (DSY) originated from the "Shi Fang Ge Kuo" is a Chinese formula composed of three medicines: Salvia miltiorrhiza (Dan-shen), Santalum album L. (Tan-xiang) and Amomum villosum Lour. (Sha-ren). It has many years of clinical experience in the prevention of myocardial fibrosis (MF). However, the specific mechanism of DSY in prevent MF is not clear. Aim of the studyThis study aimed to assess the efficacy of DSY in the prevention of MF and reveal its underlying mechanism in a rat model of MF after myocardial infarction (MI) induced by ligation of the left anterior descending branch (LAD) of the coronary artery. Materials and methodsThe blood-entry components of DSY were analyzed by UHPLC-Q-TOF-MS/MS. LAD-ligated rats were used to assess the efficacy of DSY in the prevention of MF. Network pharmacology and transcriptomics analysis were used to predict possible target signaling pathways of DSY in MF. Echocardiography, immunohistochemistry and ELISA methods were used to evaluate the cardiac functions and biochemical changes of the rats. The mRNA expressions of target genes were measured by RT-qPCR. The proteins expressions, including Collagen I, Collagen III, α-smooth muscle actin (α-SMA), matrix metallopeptidase 2 (MMP 2), matrix metallopeptidase 9 (MMP 9), transforming growth factor-β (TGF-β), protein kinase B (AKT), phospho-AKT, extracellular regulated protein kinases (ERK), phospho-ERK, c-Jun N-terminal kinase (JNK), phospho-JNK, mothers against decapentaplegic protein (Smad3), and phospho-Smad3 were detected and quantified by Western Blot. ResultsUHPLC-Q-TOF-MS/MS analysis disclosed that 20 components within DSY could be absorbed into blood of rats. DSY improved myocardial injury in the myocardial tissue of LAD-ligated rats, as evidenced by the elevation of left ventricular ejection fraction and left ventricular fractional shortening, and the decrease of the serum CK-MB and LDH levels. Network pharmacology and transcriptomics predicted that DSY could interfere biological processes, such as extracellular matrix organization, focal adhesion and ECM-receptor interaction, and modulate TGF-β mediated signaling pathways, including PI3K/AKT, MAPK, and Smad3. Further study confirmed that DSY reduced MF, accompanied by reduced TGF-β, Collagen I, Collagen III, α-SMA, MMP 2 and MMP 9. Moreover, DSY repressed the phosphorylation of AKT, MAPKs and Smad3. In addition, DSY reduced inflammation and suppressed the mRNA expressions of IL-1β, IL-6, TNF-α, COX2 and iNOS in MF rats. ConclusionsOur study demonstrated that DSY prevented MF in vivo, the action of which was probably via reducing extracellular matrix organization, focal adhesion ECM-receptor interaction and inflammation by regulating TGF-β mediated PI3K/AKT, MAPK and Smad signaling pathways.

Role Of Expanded Curb-65 Score In Predicting The Severity Of Community Acquired Pneumonia

Introduction: Assessment of severity and site of care decisions for community-acquired pneumonia patients (CAP) are very important for patients’ safety and optimal use of resources. Late admission to the intensive care unit (ICU) leads to increase the rate of mortality in CAP. We aimed to evaluate the effectiveness of the new expanded CURB-65 score in comparison with CURB-65 in predicting CAP patient outcomes. Materials and Methods: This was a cross sectional study which includes 90 patients presented with CAP in Government hospital for chest and communicable disease, AMC, Visakhapatnam Results: The study included 90 patients hospitalized with CAP of which mean (SD) age distribution is 51.49±16.63 years, with 64.4% being men and 83.3% of CAP patients had associated comorbidities. All patients (100%) had elevated serum LDH (> 230U/L), 87.8% had hypoalbuminemia, 8.9% had thrombocytopenia, and 4.44% had elevated BUN values within 24 hours of admission. Regarding outcomes, the ICU admission rate was 36.7%, the 30-day mortality rate was 14.4%, and 35.6% required mechanical ventilation. There was a significant association between tachypnea (respiratory rate >30/min), confusion, and thrombocytopenia (Platelet Count < 100×103/mm3) with 30-day mortality, according to univariate analysis. The current study found that as 30-day mortality for Expanded CURB score of (0-2), (3-4) and (5-8) is 0,4%and 9% respectively, requirement of mechanical ventilation and ICU admission rate were 2%,22%, 8% and2%,23%,8% respectively. Length of hospital stay increase as the score increase with median length of hospital stay being 7 days. Conclusion: Compared to CURB-65 and other assessment tools, the Expanded-CURB-65 score, which extends independent risk factors to 8 variables in assessing CAP severity, significantly improves identifying high-risk patients and thereby helps in early institution of appropriate therapy

Effects of cannabidiol on AMPKα2 /HIF-1α/BNIP3/NIX signaling pathway in skeletal muscle injury.

Cannabidiol: (CBD) is a non-psychoactive natural active ingredient from cannabis plant, which has many pharmacological effects, including neuroprotection, antiemetic, anti-inflammatory and anti-skeletal muscle injury. However, the mechanism of its effect on skeletal muscle injury still needs further research. In order to seek a scientifically effective way to combat skeletal muscle injury during exercise, we used healthy SD rats to establish an exercise-induced skeletal muscle injury model by treadmill training, and systematically investigated the effects and mechanisms of CBD, a natural compound in the traditional Chinese medicine Cannabis sativa L., on combating skeletal muscle injury during exercise. CBD effectively improved the fracture of skeletal muscle tissue and reduced the degree of inflammatory cell infiltration. Biochemical indexes such as CK, T, Cor, LDH, SOD, MDA, and GSH-Px in serum of rats returned to normal. Combining transcriptome and network analysis results, CBD may play a protective role in exercise-induced skeletal muscle injury through HIF-1 signaling pathway. The experimental results implied that CBD could down-regulate the expression of IL-6, NF-κB, TNF-α, Keap1, AMPKα2, HIF-1α, BNIP3 and NIX, and raised the protein expression of IL-10, Nrf2 and HO-1. These results indicate that the protective effect of CBD on exercise-induced skeletal muscle injury may be related to the inhibition of oxidative stress and inflammation, thus inhibiting skeletal muscle injury through AMPKα2/HIF-1α/BNIP3/NIX signal pathways.

Hepatoprotective Activity of Gingko biloba‐Mediated TiO2 NPs Against Acetaminophen‐Induced Albino Rats‐ In Vitro Studies

AbstractNumerous effects of “titanium dioxide nanoparticles (TiO2 NPs)” have been described and significantly utilized in complementary drugs for many decades. This study is conducted to analyze the therapeutic efficiency of TiO2 NPs against the acetaminophen‐(AMP) induced toxicity. TiO2 NPs were initially prepared using Ginkgo biloba leaf extract as reducing and stabilizing agent. The prepared TiO2 NPs were studied using various spectroscopic and microscopic techniques. AFM, TEM, XRD, and DLS studies have confirmed the formation of TiO2 NPs with size between 20 to 60 nm with negative surface charge of about −12 mV. Later, hepatoprotective studies were performed by administering AMP to albino mice only once at a dosage of 2 g/kg p.o. Post 24 h of AMP intoxication, the animals were treated orally with three different doses of TiO2 NPs (150, 100, and 50 mg/kg) or silymarin at an amount of 50 mg/kg p.o., administered only once. Post 24 h of last treatment, all the animals were surrendered to death. The group of mice administered with AMP displayed a substantial raise in the serum alkaline phosphatase (560 ± 31.90), lactate dehydrogenase (167 ± 10.17), aspartate amino transferase (251 ± 14.82), alanine amino transferase (326 + 18.96), bilirubin (2.2 ± 1.066), cholesterol (96.7 ± 6.2), and albumin (6.0 ± 1.27) in serum, which signified the liver damage. A considerably depleted level of glutathione (5.4 + 1.24) was detected in the mice intoxicated with AMP. The activities of catalase (33.2 ± 2.66) and superoxide dismutase (36 ± 2.93) declined after exposure to acetaminophen, resulting in oxidative stress in liver. The performance of adenosine triphosphatase (901 ± 50.7) and glucose‐6‐phosphatase (3.9 + 1.15) were considerably inhibited after administrating with AMP. On treating with TiO2 NPs, all the variables reversed significantly towards regular levels and were noticed to be nontoxic. The groups treated with TiO2 NPs exhibited less activity of ALT, AST, LDH, and SALP in serum, indicating the protective effect of TiO2 NPs to prevent liver damage. Exposure with TiO2 NPs inverted the cholesterol, albumin, and bilirubin levels towards normal, which is similar to silymarin treatment. TiO2 NPs exhibited a substantial change in tissue and blood biochemical parameters with that of control groups. These results indicate that TiO2 NPs possesses hepatoprotective properties that mitigate the hepatotoxicity induced by acetaminophen in rats. Hence, TiO2 NPs can be further utilized in the preparation of medicine against hepatic and renal diseases, post further clinical and preclinical studies.

Soluble cytotoxic T-lymphocyte antigen-4 (sCTLA-4) in children with immune cytopenia: relation to disease activity

Cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) is a costimulatory receptor exhibiting a potent inhibitory signal on antigen-activated immune responses. A soluble form, sCTLA-4, has been identified and was found to be increased in several autoimmune diseases. We aimed to evaluate serum levels of sCTLA-4 in different immune cytopenias, and to determine its possible relation to the disease activity. We measured serum levels of sCTLA-4 in 47 patients with immune cytopenias and compared them to 47 age- and sex-matched healthy controls. sCTLA-4 levels were significantly higher in patients with immune cytopenias compared to healthy controls (p < 0.001), however, levels were comparable between different groups of immune cytopenias (p = 0.084). Serum sCTLA-4 inversely correlated with age at diagnosis and hemoglobin level (p = 0.048, and p = 0.039 respectively), while it directly correlated with disease duration (p = 0.023) as well as markers of hemolysis including reticulocyte count, serum LDH and indirect bilirubin (p = 0.025; p = 0.019; p = 0.004 respectively). In the AIHA group, serum sCTLA-4 levels were significantly lower in patients in remission compared to patients with active disease (p = 0.026). Children with immune cytopenia exhibit significantly higher levels of circulating sCTLA-4 which correlated with disease activity, yet the prognostic significance and its use to tailor treatment regimen require additional studies.

Elevated levels of damage-associated molecular patterns HMGB1 and S100A8/A9 coupled with toll-like receptor-triggered monocyte activation are associated with inflammation in patients with myelofibrosis.

Inflammation plays a pivotal role in the pathogenesis of primary and post-essential thrombocythemia or post-polycythemia vera myelofibrosis (MF) in close cooperation with the underlying molecular drivers. This inflammatory state is induced by a dynamic spectrum of inflammatory cytokines, although recent evidence points to the participation of additional soluble inflammatory mediators. Damage-associated molecular patterns (DAMPs) represent endogenous signals released upon cell death or damage which trigger a potent innate immune response. We assessed the contribution of two prototypical DAMPs, HMGB1 and S100A8/A9, to MF inflammation. Circulating HMGB1 and S100A8/A9 were elevated in MF patients in parallel to the degree of systemic inflammation and levels increased progressively during advanced disease stages. Patients with elevated DAMPs had higher frequency of adverse clinical features, such as anemia, and inferior survival, suggesting their contribution to disease progression. Monocytes, which are key players in MF inflammation, were identified as a source of S100A8/A9 but not HMGB1 release, while both DAMPs correlated with cell death parameters, such as serum LDH and cell-free DNA, indicating that passive release is an additional mechanism leading to increased DAMPs. HMGB1 and S100A8/A9 promote inflammation through binding to Toll-like receptor (TLR) 4, whereas the former also binds TLR2. Monocytes from MF patients were shown to be hyperactivated at baseline, as reflected by higher CD11b and tissue factor exposure and increased expression levels of proinflammatory cytokines IL-1β and IL-6. Patient monocytes showed preserved TLR4 and TLR2 expression and were able to mount normal or even exacerbated functional responses and cytokine upregulation following stimulation of TLR4 and TLR2. Elevated levels of endogenous TLR ligands HMGB1 and S100A8/A9 coupled to the finding of preserved or hyperreactive TLR-triggered responses indicate that DAMPs may promote monocyte activation and cytokine production in MF, fueling inflammation. Plasma IL-1β and IL-6 were elevated in MF and correlated with DAMPs levels, raising the possibility that DAMPs could contribute to cytokine generation in vivo. In conclusion, this study highlights that, in cooperation with classic proinflammatory cytokines, DAMPs represent additional inflammatory mediators that may participate in the generation of MF inflammatory state, potentially providing novel biomarkers of disease progression and new therapeutic targets.

Association between laboratory markers, clinical and radiological findings in patients with idiopathic intracranial hypertension: case–control study

BackgroundIdiopathic intracranial hypertension (IIH) is a disease of raised intracranial pressure. Contribution of inflammatory mediators has been suggested in IIH pathophysiology. The aim of this study was to estimate certain serum inflammatory markers in IIH patients compared to normal subjects. Also, to examine the correlation between these laboratory parameters and the clinical and radiological characteristics of IIH patients.ResultsBody mass index (BMI) was significantly higher among IIH patients compared to controls. Serum LDH, CRP, NLR and PLR were significantly higher, whereas serum iron was significantly lower in IIH patients compared to healthy controls. IIH patients with stenosis in brain MRV had significantly higher mean serum CRP compared with patients with normal MRV. There was a statistically significant positive correlation between serum CRP and the presence of stenosis in MRV, between serum LDH level and grade of papilledema, and between CRP, TIBC, and NLR with BMI.ConclusionsThere is a significant elevation of inflammatory markers in IIH patients. Moreover, cerebral venous sinus stenosis and BMI were positively associated with higher markers of inflammation as CRP, LDH and NLR indicating the role of inflammation in thrombosis and obesity associated with IIH.

4-Phenylbutyric acid suppresses psoralen-induced hepatotoxicity by inhibiting ERS and reestablishing mitochondrial fusion-fission balance in mice

Psoralen is a main active molecule of the traditional Chinese herb medicine Fructus Psoraleae. Our previous studies have shown that psoralen induced liver injury through the endoplasmic reticulum stress (ERS) signaling pathways. In this article, we studied whether the ERS inhibitor, 4-phenylbutyrate acid (4-PBA) could inhibit the liver toxicity caused by psoralen, and explored the underlying mechanisms. Mice were given the solvent, 20 mg/kg, 40 mg/kg, 80 mg/kg of psoralen, or 80 mg/kg of psoralen plus 4-PBA for 14 days. We found that 4-PBA significantly reduced the serum LDH and liver tissue MDA level, increased the activities of SOD and CAT, reduced liver weight and coefficient, repaired histopathological damage, and inhibited hepatocytes apoptosis induced by psoralen. RNA-seq transcriptomics found that except for the endoplasmic reticulum, the mitochondria was severely affected by psoralen. And genes involved in mitochondrial fusion, apoptosis, protein folding, and autophagy were found differently expressed in the psoralen group. Further studies found that 4-PBA inhibited the overexpression of GRP78 and CHOP, increased the Bcl-2/Bax ratio, and reduced the expression of Caspase-3. Moreover, 4-PBA reduced the overexpression of mitochondrial fission protein DRP1, increased the expression of fusion proteins Mfn-2 and OPA1, but has no inhibitory effects on autophagy proteins Atg5 or LC3A/B. In conclusion, 4-PBA inhibited ERS and reestablished mitochondrial fusion-fission balance, thereby blocking cell apoptosis, oxidative stress, and mitochondrial dysfunction, thus prevented against psoralen-induced hepatotoxicity.

Prolyl hydroxylase inhibitor desidustat attenuates autoimmune hemolytic anemia in mice

Autoimmune hemolytic anemia (AIHA) is a heterogeneous group of diseases mediated by autoantibody directed against RBCs causing hemolysis and anemia. AIHA develops rapidly or over time, depending on the triggering factor. Desidustat is a prolyl hydroxylase inhibitor clinically used for the treatment of chronic kidney disease (CKD)-induced anemia. In this study, we investigated the effect of desidustat in preclinical model of AIHA. We used rat RBC for induction of AIHA in mice. These mice were then treated with desidustat (15 mg/kg, PO, once a day) for eight weeks. Desidustat treatment increased hemoglobin, RBC and hematocrit and decreased WBC and lymphocytes. This treatment suppressed serum LDH, oxidative stress in RBCs, antibody titer and antibody deposition on RBC surface, and increased RBC lifespan. Serum and spleen iron along with spleen mass and oxidative stress were decreased by desidustat. Bone marrow iron was increased and expression of CD71 (cell surface marker for early erythroid progenitor) and TER-119 (cell surface marker for late erythroid progenitor) in bone marrow were found to be elevated by desidustat by treatment. This treatment also suppressed deposition of membrane-bound antibody in late erythroid cells. The treatment showed reduction in total splenic cells, CD71 and TER-119 positive cells in the spleen. Thus, desidustat treatment increased erythropoiesis, early maturation of bone marrow erythroid cells having longer RBC life span due to decrease in the antibody-mediated lysis of RBCs and its progenitors leading to reduced oxidative stress. Thus, desidustat can be a good therapeutic option for treatment of AIHA.

Prognostic Role of Clinicopathological Characteristics and Serum Markers in Metastatic Melanoma Patients Treated with BRAF and MEK Inhibitors.

A total of 199 patients with advanced melanoma treated with BRAF + MEK inhibitors were included in our single-center retrospective study. We analyzed the risk of progression and death using multivariate Cox proportional hazard models. The predictive effect of prognostic factors on progression-free survival (PFS) was evaluated in ROC analysis. We found that primary tumor localization, Clark level, pT category, baseline M stage and baseline serum S100B are independent and significant prognostic factors for PFS. The discriminative power of the combination of these factors was excellent for predicting 18 month PFS (AUC 0.822 [95% CI 0.727; 0.916], p < 0.001). Primary tumor localization on the extremities, Clark level V, baseline M1c stage or M1d stage, and elevated baseline serum S100B and LDH levels were independently and significantly associated with unfavorable overall survival (OS). Baseline M stage and serum S100B appear to be independent prognostic factors for both PFS and OS in melanoma patients treated with BRAF + MEK inhibitors. We newly identified significant and independent prognostic effects of primary tumor localization and Clark level on survival that warrant further investigation.

Effects of Plasma Therapy on Laboratory Factors and Clinical Improvement of COVID-19 Patients

Objectives: Over 50 million confirmed cases and 1.5 million fatalities worldwide have been linked to the COVID-19 pandemic. Researchers have used convalescent plasma (CP) from recovered patients, which includes neutralizing antibodies, to develop therapeutics for virus neutralization and prevention. This study assessed the effectiveness of CP using several clinical and laboratory variables. Methods: The intervention group received two doses of CP on the day of hospitalization, while the control group received standard care. Clinical and analytical data were documented and evaluated before plasma therapy and on the third and fifth days after therapy. The results were measured in the patient’s blood using the ELISA method. Results: The present study showed that the ICU hospitalization times for the control and CP groups were similar, with a slightly lower mortality rate in the CP group (6.2% vs. 8.2%, p &gt; 0.05). There was no significant association between COVID-19 and clinical factors such as blood pressure, heart rate (HR), respiration rate (RR), and temperature. The blood serum urea, serum LDH, ALT, PTT, PLT, and IL-6 were significantly higher in the CP group than in the control group (p &lt;0.05). Our results indicated that there was no difference in blood pH, PO2 , HCO3 , ESR, WBC counts, serum troponin, Na, AST, CRP, D-dimer, and PT between patients in the CP and control groups. Conclusion: Overall, in certain instances, CP therapy may help individuals with COVID-19 recover. In general, additional research is required to determine the efficacy of plasma treatment in COVID-19 patient care.

Impact of JAK2 V617F mutation on disease profile and prognostic risk factors in primary myelofibrosis (MPN) - A tertiary care experience.

Objective: To evaluate the association between JAK2 mutation status, PMF disease characteristics, and prognostic features as assessed by the DIPSS Plus scoring system. We analyzed clinical and laboratory data from a cohort of PMF patients to determine the influence of JAK2 mutation on disease presentation and progression. Study Design: Cross Sectional study. Setting: Department of Pathology and Oncology, King Edward Medical University/Mayo Hospital, Lahore. Period: December 2022 to December 2023. Methods: Total 27 patients with PMF were enrolled in the study by non-probability consecutive sampling technique. Patients were diagnosed according to WHO 2016 criteria. CBC and serum LDH were performed by automated hematology and chemistry analyzers respectively. Real-time PCR was used to identify the JAK2 mutations. Risk stratification was done by DIPPS criteria. Data was analyzed by Microsoft Excel 2010. Mean and standard deviation was calculated. Student ‘T’ test was used for comparison of mean between two groups with and without JAK2 mutations. Results: Out of 27 patients 66.6% were males and median age was 59 years. Splenomegaly was the dominant clinical feature accounting for 51.4% with mean splenic span of 17.8±2.91cm. Mean LDH levels was 872.5±324. JAK2 positive expression was found to be significantly correlated with increased splenic span and raised LDH levels with P-value of &lt;0.05. Risk stratification showed 11% patients were in high-risk group. Conclusion: Marked enlargement of spleen and raised in serum LDH levels indicate that patients in our settings had clinically advanced stage of the disease. Apart from this manifestation of JAK2 V617F mutated patients indicated a more aggressive phenotype of the disease.

Female Patients with Small Cell Lung Cancer Have Better Survival than Males with Extensive but Not Limited Disease

Introduction: Several previous studies have explored whether sex has prognostic significance in patients with small cell lung cancer (SCLC). In this retrospective study, we aimed to show the clinical significance of sex in SCLC patients. Methods: A total of 378 SCLC patients were assessed retrospectively. Results: Sixty-one (16.1%) patients were women; 26 of 131 (19.9%) patients had limited disease (LD-SCLC); and 14.2% of patients (35 of 247 patients) had extended disease (ED-SCLC). In all SCLC patients, regardless of stage, female patients were more likely to be nonsmokers (7.7 vs. 1%, p = 0.04 for LD-SCLC; and 11.4 vs. 1.4%, p = 0.001 for ED-SCLC) and more often to be anemic (26.9 vs. 11.4%, p = 0.04 for LD-SCLC; and 45.7 vs. 28%, p = 0.03 for ED-SCLC). While women with LD-SCLC were diagnosed younger (<60) than men (65.4 vs. 37.1%, p = 0.009), they had larger (>5 cm) tumors (69.2 vs. 42.9%, p = 0.01). Moreover, obesity (77.1 vs. 56.4%, p = 0.02) and less weight loss (88.6 vs. 73.6%, p = 0.04) were more common in women with ED-SCLC than in men. However, there were no associations between sex and significant prognostic factors, such as performance status, metastasis site, serum LDH level, response to chemotherapy, and disease recurrence. Outcomes in LD-SCLC patients were found to be similar between sexes; median overall survivals in women compared to men was 18 versus 15 months, respectively (p = 0.8). On the other hand, female patients with ED-SCLC had better survivals; median survivals for women versus men were 10 versus 7 months, respectively (p = 0.008). This significance for female ED-SCLC patients was also maintained in the multivariate analysis (p = 0.001). Conclusion: While the survival rates of female patients, who constitute a small proportion of SCLC patients, are no different from men in LD-SCLC, they are better in ED-SCLC.

The therapeutic effect of NRF2 activator, ezetimibe, in cardiac cachexia.

Heart failure (HF) is caused by functional and structural irregularity leading to impaired ejection or filling capacity of the heart. HF leads to chronic inflammatory conditions in the heart leads to weight loss, anorexia, and muscle atrophy known as cachexia. The present study was carried out to investigate the role of Ezetimibe, an NRF2 activator, in cardiac cachexia and to develop a treatment strategy for cardiac cachexia. Balb/c mice of either sex at 6-8 weeks of age were given 2 mg/kg of doxorubicin in 0.9% sodium chloride solution intraperitoneally (i.p.) for the alternate days for the first week and then once a week for the next 4 weeks. After induction of cardiac atrophy, treatment with Ezetimibe (1.5 mg/kg, p.o) was given for the next 4 weeks. In the cardiac cachectic animals, a significant decrease in body weight, food, and water intake was observed. Cardiac cachectic animals showed a significant increase in serum glucose, total cholesterol, LDL, triglyceride, VLDL, CK-MB, LDH, and CRP levels. Cardiac atrophic index, heart weight to body weight ratios (HW/BW), right ventricular weight to heart weight ratios (RV/HW), and left ventricular weight to heart weight ratios (LV/HW), were significantly decreased in cardiac cachectic animals. The weights of the skeletal muscles such as EDL, gastrocnemius, soleus, tibialis anterior, and quadriceps muscles, and the weight of adipose tissue such as subcutaneous, visceral, perirenal, and brown adipose tissue were significantly decreased in the cardiac cachectic group relative to the normal group. Treatment with ezetimibe improves body weight, food intake, and water intake. Ezetimibe decreases serum glucose, total cholesterol, LDL, triglyceride, VLDL, CK-MB, LDH and CRP levels. Cardiac atrophic markers such as HW/BW, RV/HW, and LV/HW were improved. The weight of skeletal muscles and adipose tissue was increased after treatment with ezetimibe. Our data showed that the NRF2 activator, Ezetimibe produces a beneficial effect on cardiac cachexia in the doxorubicin-induced cardiac cachexia model. Ezetimibe was successful to reduce the levels of inflammatory cytokines, ameliorate the effects on cardiac muscle wasting, lipid levels, fat tissues, and skeletal muscles.

Deletion of Dux ameliorates muscular dystrophy in mdx mice by attenuating oxidative stress via Nrf2.

DUX4 has been widely reported in facioscapulohumeral muscular dystrophy, but its role in Duchenne muscular dystrophy (DMD) is unclear. Dux is the mouse paralog of DUX4. In Dux-/- mdx mice, forelimb grip strength test and treadmill test were performed, and extensor digitorum longus (EDL) contraction properties were measured to assess skeletal muscle function. Pathological changes in mice were determined by serum CK and LDH levels and muscle Masson staining. Inflammatory factors, oxidative stress, and mitochondrial function indicators were detected using kits. Primary muscle satellite cells were isolated, and the antioxidant molecule Nrf2 was detected. MTT assay and Edu assay were used to evaluate proliferation and TUNEL assay for cell death. The results show that the deletion of Dux enhanced forelimb grip strength and EDL contractility, prolonged running time and distance in mdx mice. Deleting Dux also attenuated muscle fibrosis, inflammation, oxidative stress, and mitochondrial dysfunction in mdx mice. Furthermore, Dux deficiency promoted proliferation and survival of muscle satellite cells by increasing Nrf2 levels in mdx mice.

The impact of PPAR-γ/Nrf-2/HO-1, NF-κB/IL-6/ Keap-1, and Bcl-2/caspase-3/ATG-5 pathways in mitigation of DOX-induced cardiotoxicity in an animal model: The potential cardioprotective role of oxyresveratrol and/or dapagliflozin

Antioxidants given concurrently with chemotherapy offer an effective strategy for reducing the negative effects of the drug. One remaining obstacle to the use of doxorubicin (DOX) in chemotherapy is cardiotoxicity. Using vitamin E (Vit. E) as a reference standard, our study focuses on the potential preventive benefits of oxyresveratrol (ORES) and/or dapagliflozin (DAPA) against DOX-induced cardiac injury. Acute cardiotoxicity was noticed after a single intravenous injection of a male rat's tail vein with 10 mg/kg of DOX. Oral doses of ORES (80 mg/kg), DAPA (10 mg/kg), and Vit. E (1 g/kg) were given, respectively. Pretreatment of animals with Vit. E, ORES and/or DAPA revealed a considerable alleviation of heart damage, as evidenced by histopathological change mitigation and a notable drop in serum AST, LDH, CK, CK-MB, and cardiac contents of MDA and NO2−. Also, serum TAC, tissue GSH, and SOD showed substantial increases. Additionally, tissue caspase-3, serum IL-6, and TNF-α were considerably reduced. Moreover, a downregulation in cardiac gene expression of ATG-5, Keap-1, and NF-κB in addition to an upregulation of Bcl-2 gene expression and HO-1, Nrf-2, and PPAR-γ protein expression clearly appeared. Ultimately, ORES and/or DAPA have an optimistic preventive action against severe heart deterioration caused by DOX.

Physiological biodistribution on Ga68-PSMA PET/CT and the factors effecting biodistribution

AimThe study aims to determine the physiological and pathophysiological distribution of the radiopharmaceutical (Ga68-PSMA-617) and investigate whether there are differences in distribution according to the laboratory, histopathological and clinical findings that can affect image evaluation. Also, we aimed to determine cut-off values to distinguish physiological and pathological uptake in prostate, bone, and lymph nodes.Materials and Methods229 prostate cancer patients who underwent Ga68-PSMA PET/CT at our department were retrospectively analyzed. The patients were grouped according to PET/CT results, Gleason scores, PSA values, received treatments, metastatic status and other laboratory values. The SUV values of the organs, tissues, and pathological lesions of the patients in these subgroups were compared among themselves.ResultsNo significant difference was detected in the physiological uptake of lymph nodes and bone between the groups. In the group with patients that received androgen deprivation therapy (ADT), the bone metastasis SUV values were found to be higher and the SUV values of the submandibular gland and renal cortex were found to be lower (Mann–Whitney U, p = 0.043; 0.004; 0.01, respectively). In the group with patients who received radiotherapy, the normal prostate tissue SUV values were determined to be higher (Mann–Whitney U, p = 0.009). The SUV values of the submandibular gland, muscle, liver, and blood pool were found to be lower in the group of patients with high serum LDH values. The cut-off SUVmax value was determined to be 6.945 (sensitivity 89.6%, specificity 98.1%) for primary prostate lesion; 4.72 for lymph node metastasis; 4.25 for bone metastasis. The serum PSA cut-off value to distinguish the negative/positive groups was found to be 1,505 (sensitivity 79.7%, specificity 77.3%).ConclusionIn conclusion, PSMA-617 demonstrates a similar biodistribution with other PSMA ligands. The physiological uptake of lymph nodes and bone which are mostly metastasized in prostate cancer, are not affected by the factors we examined. It should be kept in mind that the normal prostate tissue uptake may increase in patients receiving radiotherapy, and the physiological/pathological uptake of the organs may differ due to the changes in PSMA expression in patients receiving ADT, tumor burden, and kidney function may affect the biodistribution.

A retrospective study of prognostic factors and treatment outcome in advanced-stage Mycosis Fungoides and Sezary Syndrome

ABSTRACT Background: Mycosis fungoides (MF) and Sezary Syndrome (SS) comprise over half of all Cutaneous T-cell lymphoma diagnoses. Current risk stratification is largely based on TNMB staging, few research investigated the prognostic value of clinical exams. Current systemic therapy for advanced disease includes immunomodulatory drugs, chemotherapy, and HADC inhibitors. Few clinical trials or retrospective research compared the efficacy of different drugs. Method: Here, we performed a retrospective analysis of prognostic factors and treatment outcomes of 92 patients diagnosed with MF/SS at the Peking Union Medical College Hospital from 2013-2023. Results: Cox regression analysis identified that age ≥ 50 years, WBC ≥ 8 × 109/L, serum LDH ≥ 250U/L, β2-MG ≥ 4.50 mg/L, and stage IV were associated with reduced overall survival, age ≥ 50 years, serum LDH ≥ 250U/L and stage IV were associated with reduced progression free survival. Kaplan-Meier analysis established that immunomodulatory therapy was associated with longer progression free survival. Conclusion: These results suggested new factors in predicting prognosis and selecting appropriate treatments in patients with advanced MF/SS.